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Sodium and water homeostasis is maintained in rats with chronic TRPV4 blockade
Author(s) -
Costell Melissa H.,
Bernard Roberta E.,
McCafferty Gerald P.,
Roethke Theresa J.,
Jolivette Larry J.,
Willette Robert N.,
Cheung Mui,
Thorneloe Kevin S.,
Schnackenberg Christine G.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1079.17
Subject(s) - chemistry , endocrinology , vasopressin , medicine , cotransporter , homeostasis , sodium , furosemide , blockade , kidney , diuretic , renal function , epithelial sodium channel , blood pressure , pharmacology , receptor , biochemistry , organic chemistry
The transient receptor potential vanilloid 4 (TRPV4) is a non‐selective cation channel that highly expressed in renal tubules. Co‐localization of TRPV4 with sodium transporters suggests that TRPV4 might have a role in the regulation of sodium and water homeostasis. To investigate this potential interaction, we determined the blood pressure and renal responses to chronic TRPV4 blockade (GSK2193874A, 30 mg/kg/d) in rats in the presence and absence of Na, K,2Cl − cotransporter, Na, Cl cotransporter, or arginine vasopressin V 2 receptor (AVP‐V2) inhibition. Under normal conditions, TRPV4 blockade had no effect on mean arterial pressure, renal excretory function, free water clearance, or plasma sodium concentrations. The diuretic and natriuretic responses to Na, K,2Cl − cotransporter inhibition (furosemide, 30 mg/kg) or Na, Cl cotransporter inhibition (hydrochlorothiazide, 30 mg/kg) were unaltered after 5 days of TRPV4 blockade. In contrast, GSK2193874A increased the diuretic, natriuretic, and plasma sodium responses to AVP‐V2 inhibition (tolvaptan, 10 mg/kg). Further investigation showed that GSK2193874A increased the plasma concentration of tolvaptan which accounted for the enhanced renal response. In conclusion, TRPV4 has no major effect on blood pressure or sodium and water homeostasis in normal rats either directly or through modulation of sodium transporter or AVP‐V2 function in the kidney.